Impact of minimal solid and micropapillary components on invasive lung adenocarcinoma recurrence.

BACKGROUND: The specific impacts of solid and micropapillary components on prognosis in lung adenocarcinoma remain unclear. Herein, we elucidated their distinct contributions to lung adenocarcinoma recurrence. MATERIALS AND METHODS: Lung adenocarcinoma was classified into solid and micropapillary absent (S-M-); solid absent, micropapillary present (S-M+); micropapillary absent, solid present (S + M-); and solid and micropapillary present (S + M+). Cumulative incidence of recurrence (CIR) was calculated using competing risk analysis. RESULTS: Of 994 adenocarcinomas, 650 (65.4%) were classified as S-M-; 152 (15.3%), S-M+; 148 (14.9%), S + M-; and 44 (4.4%), S + M+. In total, 168 (16.9%) patients had recurrence; 16 (1.6%) died from other causes. S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P < 0.001, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- had significantly higher CIR than S-M+ (P = 0.002). These differences remained significant in multivariable analysis. In stage IA, S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P = 0.006, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- and S + M+ had significantly higher CIR than S-M+ (P = 0.005, P = 0.008, respectively). These differences remained significant in multivariable analysis. CIR was not significantly different between S + M- and S-M+ subgroups. CONCLUSIONS: The presence of solid or micropapillary component (≥1%) was an independent risk factor for CIR; patients with solid component alone had a higher CIR than those with micropapillary component alone. In IA lung adenocarcinoma, patients with both solid and micropapillary components had a higher CIR than those with micropapillary component alone; the proportion of solid or micropapillary component was not associated with CIR.

Association of lymph node involvement with the prognosis of pathological T1 invasive non-small cell lung cancer.

BACKGROUND: Lymph node involvement could help to predict the prognosis of pathological T1 (pT1, diameters of ≤3 cm) non-small cell lung cancer (NSCLC). This study assessed the clinicopathological factors and associated lymph node involvement in invasive lung adenocarcinoma (IAC) and squamous cell lung cancer (SCC) and the overall and disease-free survival associated with these factors. METHODS: Three hundred and twenty-five patients with pathological T1 NSCLC (253 IAC and 72 SCC) were retrospectively analyzed from a pool of 1094 primary lung cancer patients. The data were assessed using multiple logistic regression, Kaplan-Meier curves and multivariable analyses. RESULTS: Among patients with a ≤30-mm tumor lesion (N = 325), N1 and N2 lymph node involvement was found in 28 (8.6%) and 34 (10.4%) patients, respectively. Lymph node metastasis occurred in 13.0% (33/253) of pT1 IAC patients and 40.3% (29/72) of SCC patients. Carcinoembryonic antigen (CEA) levels, SCC by histology, and tumor lesions larger than 1.0 cm were associated with lymph node involvement (P < 0.0001, <0.0001, and 0.048, respectively). In IAC patients, negative lymph nodes were associated with better overall survival compared with lymph node-positive ones (P = 0.021). No significant difference was observed in SCC patients regardless of lymph node status (P = 0.40). Multivariable Cox analysis revealed that lymph node involvement was an independent prognostic predictor of overall IAC patient survival (P = 0.041), but not of SCC patient survival (P = 0.470). Chemotherapy was administered to 72.2% (52/72) of SCC patients, a significantly higher rate when compared with that of IAC patients (42.3%, 107/253). CONCLUSIONS: Lymph node metastasis was inversely associated with the overall survival of IAP patients, but not with the survival of SCC patients. Patients with pT1 SCC exhibited a significantly higher rate of lymph node involvement when compared with IAC patients. Thus, a systematic lymph node dissection should be performed in pT1 IAC patients, especially in patients with IAC larger than 1.0 cm, for additional treatment selections to improve survival.

Differential expression of miR-125a-5p and let-7e predicts the progression and prognosis of non-small cell lung cancer.

Aberrant expression of various microRNAs (miRNA) has shown diagnostic and prognostic significance in non-small cell lung cancer (NSCLC). qRT-PCR analysis confirmed altered expression of miR-125a-5p, let-7e, miR-30a, miR-30e and miR-30e-3p in 70 paired tissue and serum samples from NSCLC patients. The reduced expression of miR-125a-5p, let-7e and miR-30e was strongly associated with NSCLC dedifferentiation. The lost expression of miR-125a-5p and let-7e was associated with shorter overall survival and let-7e was an independent prognostic factor for NSCLC patients. These five miRNA expressions should be further evaluated as biomarkers for the early detection and prognosis of NSCLC patients.

Identification of a Plasma Exosomal lncRNA- and circRNA-Based ceRNA Regulatory Network in Patients With Lung Adenocarcinoma.

BACKGROUND: Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA- and circRNA-mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive. METHODS AND RESULTS: This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA-miRNA-mRNAs/circRNA-miRNA-mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT-qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT-qPCR validated that the expression of circ-0033861, circ-0043273, and circ-0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively). CONCLUSION: This study proposed a newly discovered ncRNA-miRNA-mRNA/circRNA-miRNA-mRNA ceRNA network and identified that the expression of circulating circ-0033861, circ-0043273, and circ-0011959 was up-regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.

Pathological and imaging features of pulmonary invasive mucinous adenocarcinoma-a retrospective cohort study.

Background: Pulmonary invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung cancer which is easily misdiagnosed as inflammatory nodules, tuberculosis, pulmonary diffuse lesions, or hamartomas due to the lack of clinical specificity. This study aims to identify the pathological and imaging characteristics of IMA, which will favor to improve the diagnostic and therapeutic efficacy. Methods: A retrospective study was conducted by enrolling patients histopathologically diagnosed with pulmonary IMA in the current study between January 2014 and December 2021. The clinical pathological and radiological data were collected for analysis to evaluate the radiological patterns and pathological and molecular characteristics of IMA. Results: A total of 136 patients were included in the study, of whom 58 were male and 78 were female. The patients had an average age of 63.0±9.7 years. The tumors were classified into the following three pathological types: pure mucinous (76 cases) featured by only mucinous cells observed under the microscope; mixed mucinous (23 cases) featured as an attached-wall, papillary, acinar, and solid tumor cells with more than 10% mucinous cells.; and mucinous-absent (29 cases) featured with the absence of mucous cells, but still can detect more than 10% of mucin expresses. In terms of the morphological classification based on the CT scans, 88 (64.7%) cases were identified as the nodular type, 31 (22.8%) as the inflammatory type, 15 (11.1%) as the mass-like type, and two (1.5%) as the diffuse type. For the molecular features, patients afflicted with IMA showed much lower levels of thyroid transcription factor-1 (15%) than those with usual adenocarcinoma (over 80%). However, cytokeratin 20 was more common in IMA (50%) than the usual adenocarcinoma (about 5%). The K-RAS mutation was prevalent in 75% of IMA, which contrasted sharply to its occurrence in a mere 15% of the usual adenocarcinoma. Epidermal growth factor receptor mutations were rarer in IMA (less than 5%) than the usual adenocarcinoma (about 50%). Conclusions: The pathological and imaging features enrich our understanding of the disease's heterogeneity, which will contribute to more personalized diagnostic and therapeutic strategies.

Evaluation of the preoperative neutrophil-to-lymphocyte ratio as a predictor of the micropapillary component of stage IA lung adenocarcinoma.

OBJECTIVE: To assess the ability of markers of inflammation to identify the solid or micropapillary components of stage IA lung adenocarcinoma and their effects on prognosis. METHODS: We performed a retrospective study of clinicopathologic data from 654 patients with stage IA lung adenocarcinoma collected between 2013 and 2019. Logistic regression analysis was used to identify independent predictors of these components, and we also evaluated the relationship between markers of inflammation and recurrence. RESULTS: Micropapillary-positive participants had high preoperative neutrophil-to-lymphocyte ratios. There were no significant differences in the levels of markers of systemic inflammation between the participants with or without a solid component. Multivariate analysis showed that preoperative neutrophil-to-lymphocyte ratio (odds ratio [OR] = 2.094; 95% confidence interval [CI], 1.668-2.628), tumor size (OR = 1.386; 95% CI, 1.044-1.842), and carcinoembryonic antigen concentration (OR = 1.067; 95% CI, 1.017-1.119) were independent predictors of a micropapillary component. There were no significant correlations between markers of systemic inflammation and the recurrence of stage IA lung adenocarcinoma. CONCLUSIONS: Preoperative neutrophil-to-lymphocyte ratio independently predicts a micropapillary component of stage IA lung adenocarcinoma. Therefore, the potential use of preoperative neutrophil-to-lymphocyte ratio in the optimization of surgical strategies for the treatment of stage IA lung adenocarcinoma should be further studied.

Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) is one of the major causes of cancer­related death worldwide. Cisplatin is a front­line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin­mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription­quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS­mediated endoplasmic reticulum stress, and the C­Jun­amino­terminal kinase and p38 mitogen­activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS­mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.

Increased TIM-3 expression in tumor-associated macrophages predicts a poorer prognosis in non-small cell lung cancer: a retrospective cohort study.

Background: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is considered a key negative regulator in T-cell-mediated response. However, few studies have been reported on the relationship between TIM-3 expression in tumor-associated macrophages (TAMs) and clinicopathological characteristics of patients. This study evaluated the correlation between the expression of TIM-3 on the surface of TAMs macrophages in tumor matrix and the clinical outcome of patients with non-small cell lung cancer (NSCLC). Methods: The expression of CD68, CD163 and TIM-3 in 248 NSCLC patients who underwent surgery in Zhoushan Hospital from January 2010 to January 2013 was detected by immunohistochemistry (IHC). From the date of operation to the date of death, overall survival (OS) was measured to analyze the relationship between the expression of Tim-3 and the prognosis of NSCLC patients. Results: The study assessed 248 patients with NSCLC. TIM-3 expression in TAMs was more frequently identified in patients with higher carcinoembryonic antigen (CEA) levels, lymph node metastasis, higher grade, high CD68 expression, and high CD163 expression (P<0.05). The OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups (P=0.01). Patients with high TIM-3 and CD68/CD163 expressions had the worst prognosis, whereas patients with low expressions of both TIM-3 and CD68/CD163 had the best prognosis (P<0.05). In NSCLC, the OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups (P=0.01). In lung adenocarcinoma, the OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups(P=0.03). Conclusions: TIM-3 expression in TAMs may be a promising prognostic biomarker for NSCLC or adenocarcinoma. Our results demonstrated that high TIM-3 expression in TAMs was an independent predictor of worse prognosis in patients.

miR-31/QKI-5 axis facilitates cell cycle progression of non-small-cell lung cancer cells by interacting and regulating p21 and CDK4/6 expressions.

BACKGROUND: RNA-binding protein Quaking-5 (QKI-5), a major isoform of QKIs, inhibits tumor progression in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of QKI-5 in the cell cycle of NSCLC are still largely unknown. METHODS: MTT, flow cytometry, and colony formation assays were used to investigate cellular phenotypic changes. Mice xenograft model was used to evaluate the antitumor activities of QKI-5. Co-immunoprecipitation, RNA immunoprecipitation (RIP), and RIP sequencing were used to investigate protein-protein interaction and protein-mRNA interaction. RESULTS: The QKI-5 expression was downregulated in NSCLC tissues compared with that in paired normal adjacent lung tissues. Overexpression of QKI-5 inhibited NSCLC cell proliferative and colony forming ability. In addition, QKI-5 induced cell cycle arrest at G0/G1 phase through upregulating p21Waf1/Cip1 (p21) expression and downregulating cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6 expressions. Further analyses showed that QKI-5 interacts with p21 protein and CDK4, CDK6 mRNAs, suggesting a critical function of QKI-5 in cell cycle regulation. In agreement with in vitro study, the mouse xenograft models validated tumor suppressive functions of QKI-5 in vivo through altering cell cycle G1-phase-associated proteins. Moreover, we demonstrated that QKI-5 is a direct target of miR-31. The QKI-5 expression was anticorrelated with the miR-31 expression in NSCLC patient samples. CONCLUSION: Our results suggest that the miR-31/QKI-5/p21-CDK4-CDK6 axis might have critical functions in the progression of NSCLC, and targeting this axis could serve as a potential therapeutic strategy for NSCLC.

Intraoperative localization in minimally invasive surgery for small pulmonary nodules: a retrospective study.

BACKGROUND: Small pulmonary nodules are increasingly detected at an earlier stage and need to be removed via video-assisted thoracoscopic surgery (VATS). However, small pulmonary nodules are often difficult to locate during VATS and are typically nonvisible and nonpalpable on the lung surface. A variety of localization techniques have been developed. Here, we explored the application of an intraoperative body surface localization (IOBSL) and/or anatomical landmark localization (ALL) in minimally invasive surgery for small pulmonary nodules. METHODS: A total of 174 patients with small pulmonary nodules were divided into 3 groups: an IOBSL group, an ALL group, and an IOBSL+ALL group. VATS partial pneumonectomy was performed after the nodule localization, and the need for pulmonary segmentectomy/lobectomy and lymph node dissection was assessed according to the results of intraoperative rapid frozen section diagnosis. The duration, accuracy, and complications of each localization method were recorded and analyzed. RESULTS: ALL had shorter distance to the nodules (P=0.0282) but longer localization duration (P<0.05) than did IOBSL. The IOBSL+ALL group had higher localization accuracy than did the other 2 groups (P=0.0003) but with longer localization duration (P<0.001). No intraoperative complications were noted. CONCLUSIONS: The intraoperative technique has high localization accuracy and a low complication rate. It can be applied in VATS for pulmonary nodules, depending on the specific locations of the nodules.

[Enhancement pattern of thyroid carcinoma with contrast-enhanced ultrasound].

OBJECTIVE: To investigate the enhancement pattern of thyroid carcinoma with contrast-enhanced ultrasound (CEUS) for the diagnostic value. METHODS: Thirty-one cases with thirty-five thyroid Occupied were retrospectively reviewed. The final diagnosis was confirmed by biopsy pathology. Contrast agent SonoVue and contrast pulse sequencing (CPS) technique were used in this study. RESULTS: Thirty-five thyroid carcinoma presented three enhancement patterns with CEUS. Type I: twenty-three lesions enhanced in a pattern of ring with centripetal fill-in, however, the central part of no contrast agent filling. Type II: five lesions enhanced regularly and homogeneously. Type III: seven lesions enhanced irregularly and homogeneously. Thyroid benign and malignant lesions perfusion time curve, compared to papillary thyroid carcinoma with nodular goiter in the AT, TTP and WT indicators P < 0.05; papillary thyroid carcinoma and thyroid adenoma, compared to WT alone an indicator of P < 0.05. CONCLUSIONS: Identification of the different enhancement patterns of thyroid carcinoma could improve the diagnostic ability of CEUS.

Cancer-associated fibroblasts, matrix metalloproteinase-9 and lymphatic vessel density are associated with progression from adenocarcinoma in situ to invasive adenocarcinoma of the lung.

The present study aimed to investigate the roles of cancer-associated fibroblasts (CAFs), matrix metalloproteinase-9 (MMP-9) and lymphatic vessel density (LVD) during the progression from adenocarcinoma in situ (AIS) to invasive lung adenocarcinoma (IAC). A total of 77 patients with stage 0-IA lung adenocarcinoma were enrolled. The expression levels of α-smooth muscle actin, MMP-9 and D2-40 were immunohistochemically analyzed. Survival analysis was performed using the Kaplan-Meier method. In the non-invasive component, the proportion of CAFs and the expression levels of MMP-9 increased from AIS to IAC; however, the LVD was not significantly different. CAFs were positively correlated with levels of MMP-9. The LVD had no significant correlation with CAFs and MMP-9. In the invasive component, CAFs, MMP-9 and LVD were significantly higher in IAC compared with in minimally invasive adenocarcinoma. CAFs, MMP-9 and LVD were all positively correlated with each other. The micropapillary subtype in IAC was associated with overall survival (OS). The LVD in IAC, but not MMP-9 and CAFs, was associated with OS. CAFs, MMP-9 and LVD were involved in the progression from AIS to IAC. CAFs exhibited a strong association with MMP-9 levels in the non-invasive and invasive components. The increase in the proportion of CAFs and the expression levels of MMP-9 may have been an early event before the adenocarcinoma became invasive. Once the adenocarcinoma was invasive, the LVD served an important role in tumor invasion and metastasis, and hence may be used as a prognostic marker of poor OS in stage IA IAC.

A Prediction Rule for Overall Survival in Non-Small-Cell Lung Cancer Patients with a Pathological Tumor Size Less Than 30 mm.

We sought to develop and validate a clinical nomogram model for predicting overall survival (OS) in non-small-cell lung cancer (NSCLC) patients with resected tumors that were 30 mm or smaller, using clinical data and molecular marker findings. We retrospectively analyzed 786 NSCLC patients with a pathological tumor size less than 30 mm who underwent surgery between 2007 and 2017 at our institution. We identified and integrated significant prognostic factors to build the nomogram model using the training set, which was subjected to the internal data validation. The prognostic performance was calibrated and evaluated by the concordance index (C-index) and risk group stratification. Multivariable analysis identified the pathological tumor size, lymph node metastasis, and Ki-67 expression as independent prognostic factors, which were entered into the nomogram model. The nomogram-predicted probabilities of OS at 1 year, 3 years, and 5 years posttreatment represented optimal concordance with the actual observations. Harrell's C-index of the constructed nomogram with the training set was 0.856 (95% CI: 0.804-0.908), whereas TNM staging was 0.814 (95% CI: 0.742-0.886, P = 5.280221e - 13). Survival analysis demonstrated that NSCLC subgroups showed significant differences in the training and validation sets (P < 0.001). A nomogram model was established for predicting survival in NSCLC patients with a pathological tumor size less than 30 mm, which would be further validated using demographic and clinicopathological data. In the future, this prognostic model may assist clinicians during treatment planning and clinical studies.

Prognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer.

INTRODUCTION: The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct. MATERIAL AND METHODS: Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations. RESULTS: Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P<0.001 and<0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and <0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P<0.0001 and 0.0009, and P<0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF-1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022). CONCLUSION: The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.

SPINK1 promotes cell growth and metastasis of lung adenocarcinoma and acts as a novel prognostic biomarker.

Serine protease inhibitor Kazal type 1 (SPINK1) plays a role in protecting the pancreas against premature activation of trypsinogen and is involved in cancer progression. SPINK1 promoted LAC cells growth, migration, and invasion. Mechanistically, we found that SPINK1 promoted LAC cells migration and invasion via up-regulating matrix metalloproteinase 12 (MMP12). We observed that SPINK1 expression was only up-regulated in lung adenocarcinoma (LAC) tissues, and was an independent prognostic factor for poor survival. Our results indicate that SPINK1 might be a potential biomarker for LAC that promotes progression by MMP12. [BMB Reports 2018; 51(12): 648-653].

A retrospective clinicopathological study of lung adenocarcinoma: Total tumor size can predict subtypes and lymph node involvement.

PURPOSE: To analyze the predictive ability of total tumor size in lung adenocarcinoma subtype and lymph node involvement. MATERIALS AND METHODS: 1018 patients, ≤3cm tumor, were enrolled. The maximum diameter and other variables of each tumor were measured. RESULTS: The optimal cut-off value for total tumor size in differentiating AIS and MIA from IAC was <1.15cm, in distinguishing lymph node involvement, it was 1.65cm. CONCLUSIONS: Total tumor size could be a reliable predictor of lung adenocarcinoma subtype and lymph node involvement irrespective of ground glass, part solid and solid characteristics.

Epidermal Growth Factor Receptor Mutations and Their Prognostic Value with Carcinoembryonic Antigen in Pathological T1 Lung Adenocarcinoma.

AIMS: The prognostic value of epidermal growth factor receptor (EGFR) mutations in the context of serum carcinoembryonic antigen levels remains controversial in T1 lung adenocarcinoma. METHODS: Clinical and pathological characteristics, preoperational carcinoembryonic antigen levels, EGFR mutations, and disease-free and overall survival were analysed retrospectively in 573 pathological T1 patients in East China. RESULTS: EGFR mutations were detected in 220 of 573 patients (38.4%). Patients with serum carcinoembryonic antigen levels ≥ 2.12 ng/mL had worse disease-free (P < 0.001) and overall survival (P < 0.001) than had others, although survival was comparable between patients with and without EGFR mutations. However, patients with exon 21 mutations in EGFR had significantly better overall survival than had patients with exon 19 mutations (P = 0.016), although disease-free survival was comparable (P = 0.424). Among patients with serum carcinoembryonic antigen levels ≥ 2.12 ng/mL, disease-free (P = 0.019) and overall survival (P < 0.001) was also better than that in those with exon 21 mutations. Finally, the exon 19 deletion was found to be an independent predictor of unfavourable overall survival (P = 0.037). CONCLUSIONS: EGFR mutations were associated with preoperational serum carcinoembryonic antigen levels ≥ 2.12 ng/mL. In patients with levels above this threshold, those with the exon 19 deletion have less favourable prognosis than have those with the exon 21 mutation.

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA-135b overexpression are more likely to invade visceral pleura.

Lung adenocarcinoma, characterized by its early and aggressive local invasion and high metastatic potential, is the most frequently observed histological type of non-small-cell lung cancer (NSCLC). Visceral pleural invasion (VPI) caused by peripheral lung adenocarcinomas is closely associated with the poor prognosis of patients with NSCLC. The association between VPI and some clinicopathological characteristics has been observed in the past few decades. However, the molecular mechanism of VPI in lung adenocarcinomas is unknown. In the present, the expression level of microRNA (miR-)135b and epidermal growth factor receptor (EGFR) mutations using the reverse transcription-quantitative polymerase chain reaction and DNA sequencing, respectively. In addition, the present study aimed at exploring the association between the miR-135b level, EGFR mutations and VPI in peripheral lung adenocarcinoma. The results of the present study demonstrated that miR-135b was significantly upregulated in lung adenocarcinoma compared with adjacent normal tissue and positively associated EGFR mutations in peripheral lung adenocarcinoma. Furthermore, it was identified that lung adenocarcinomas with EGFR mutations and miR-135b overexpression were more likely to invade visceral pleura. Taken together, these findings indicate that miR-135b overexpression is positively associated with mutations to EGFR, which may promote the development of peripheral lung adenocarcinomas by the formation of VPI. This indicates that the two factors may serve as prognostic markers and molecular targets for the treatment of peripheral lung adenocarcinomas.

[Study on relationship between blood supply from pulmonary artery and pathological characteristics of patients with primary bronchogenic carcinoma].

BACKGROUND: At present, it has been known that the bronchogenic artery participates in the blood supply of primary bronchogenic carcinoma, but there is controversy about the blood supply from pulmonary artery in primary bronchogenic carcinoma. The aim of this study is to assess the relationship between the blood supply from pulmonary artery and pathological characteristis of patients with primary bronchogenic carcinoma. METHODS: The pulmonary arteries in 43 surgical samples of bronchogenic carcinoma were marked, then the iopromide was used to selective pulmonary arteriography in digital subtraction angiography (DSA). The relationship between tumor with blood supply from pulmonary artery and the pathologic characteristics was observed. RESULTS: There were 34 samples with blood supply from pulmonary artery ( 79.07%) , and 9 samples without blood supply from pulmonary artery (20.93%). The development rate of peripheral lung cancer (100.00%) was significantly higher than that of central lung cancer (64.00%) (P < 0.01) . The development rate of squamous cell carcinoma (91.30%) was remarkably higher than that of adenocarcinoma (61.11%) (P < 0.05). The development rate of poorly differentiated lung cancer (95.00%) was remarkably higher than that of well and moderately differentiated lung cancer (65.22%) (P < 0.05). There was a positive relationship between the tumor size and the development rate (P < 0.05). CONCLUSIONS: In primary bronchogenic carcinoma, the pulmonary artery blood supply exists in most of tumors. There is relationship between the blood supply from pulmonary artery and general type, histopathology, cell differentiation and tumor size of lung cancer. The blood supply from pulmonary artery doesn't relate to tumor stage.

Diagnostic Value of Serum miR-182, miR-183, miR-210, and miR-126 Levels in Patients with Early-Stage Non-Small Cell Lung Cancer.

Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early. We investigated the serum levels of four different miRNAs in patients with non-small cell lung cancer (NSCLC) and assessed their diagnostic value for NSCLC. Serum samples from 112 NSCLC patients and 104 controls (20 current smokers without lung cancer, 23 pneumonia patients, 21 gastric cancer patients, and 40 healthy controls) were subjected to Taqman probe-based quantitative reverse transcription-polymerase chain reaction (RT-PCR). The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls. Further receiver operating characteristic (ROC) curve analysis revealed that the serum miR-182, miR-183, miR-210, or miR-126 level could serve as a diagnostic biomarker for NSCLC early detection, with a high sensitivity and specificity. The combination of these four miRNAs with carcinoembryonic antigen (CEA) further increased the diagnostic value, with an area under the curve (AUC) of 0.965 (sensitivity, 81.3%; specificity, 100.0%; and accuracy, 90.8%) using logistic regression model analysis. In addition, the relative levels of serum miR-182, miR-183, miR-210, and miR-126 could distinguish NSCLC or early-stage NSCLC from current tobacco smokers without lung cancer and pneumonia or gastric cancer patients with a high sensitivity and specificity. Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis.